Biological drugs (hereinafter, referred to as “drugs”) such as protein drugs, including antibody drugs, derived from a gene recombinant are drugs derived from an artificially produced antibody or substance specifically reactive with a disease-related molecule or receptor. Molecular-targeted treatment with a drug to control a targeted molecule or the like relating to the cause of a disease with pinpoint accuracy has become widely used in recent years, and currently 47 antibody drugs have been approved in Japan, U.S., and Europe. Most of them target cancers or autoimmune diseases, and quite a lot of products have become essential for treatment of such diseases.
However, antibody drugs induce production of ADAs due to the immune response of a patient to cause loss of response (LOR), even if the antibody drug is a humanized antibody or substance, which disadvantageously complicates disease control. Thus, required in the art is a measurement system to detect the presence of ADAs in a sample from a patient for monitoring of molecular-targeted therapy with a drug and guidance for therapeutic decision-making. Non-antibody drugs derived from a gene recombinant or the like, such as erythropoietin (Non Patent Literature 1), and other drugs also suffer from LOR or the like due to production of ADAs (Non Patent Literature 2).
In the case of infliximab (IFX), which is a representative antibody drug targeting TNF-α, for example, antibodies to IFX (ATI) appear after administration. Regarding measurement of ATI, an ATI measurement method by using double antigen assay with enzyme-linked immunosorbent assay (ELISA) (Non Patent Literature 3) and a mobility shift method in which a labeled IFX is added to a pre-treated sample and HPLC is used for the resultant (Non Patent Literature 4) are conventionally known.
However, the double antigen assay method, in which ATI are captured by IFX as a coating and the captured ATI are detected and measured with labeled IFX, may be influenced by IFX present in an analyte, which makes accurate measurement difficult. The mobility shift method requires introduction of HPLC, which is an expensive instrument, and thus is not easily applicable.